System and method for non-invasive monitoring of hemoglobin

ABSTRACT

A method of non-invasively monitoring hemoglobin concentration includes providing incident light to patient tissue at a first excitation wavelength. The method further includes monitoring a first emission response at a first emission wavelength, wherein the first emission wavelength is selected to correspond with a maximum of the emission response, and monitoring a second emission response at a second emission wavelength, wherein the second emission wavelength is selected to correspond with a minimum of the emission response. A hemoglobin concentration is calculated based on a ratio of the first emission response to the second emission response.

TECHNICAL FIELD

This invention relates generally to patient diagnosis and monitoring,and in particular non-invasive diagnosis and monitoring of hemoglobinconcentrations.

BACKGROUND

Hemoglobin (Hb) is the iron-containing protein found in blood and is thecomponent responsible for transporting gases throughout the body, suchas oxygen and carbon dioxide. Measuring hemoglobin concentration is auseful tool in screening patients for diseases such as anemia.Typically, hemoglobin concentration measurements require a blood sampleto be taken from a patient, which is sent to a lab for analysis toisolate and measure the concentration of Hb in the patient's blood.Results typically take 1-2 days to obtain, and are based on the Hblevels in the patient at the time blood is drawn. As a result, it is notfeasible to monitor Hb levels continuously over long periods of time.

It would therefore be advantageous to develop a device that is capableof detection and long-term monitoring of Hb concentration (as well asother blood components such as hematocrit, HbA1C, advanced glycation end(AGE) products), which would allow for the detection of acute conditionsas well as chronic conditions that change slowly over time.

SUMMARY

A method of non-invasively monitoring hemoglobin concentration includesproviding incident light to patient tissue at a first excitationwavelength. The method further includes monitoring a first emissionresponse at a first emission wavelength, wherein the first emissionwavelength is selected to correspond with a maximum or dominantwavelength of the emission response, and monitoring a second emissionresponse at a second emission wavelength, wherein the second emissionwavelength is selected to correspond with a minimum or a significantwavelength of the emission response. A hemoglobin concentration iscalculated based on a ratio of the first emission response to the secondemission response.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a schematic view of a patient and a patientmonitoring system, according to some embodiments.

FIGS. 2A-2C are perspective views of an adherent monitoring deviceaccording to some embodiments.

FIG. 3 is a perspective view of an insertable monitoring deviceaccording to some embodiments.

FIG. 4 is a block diagram illustrating components utilized to monitoroptical signals and processing optical signals according to someembodiments.

FIG. 5 is a flowchart that illustrates steps utilized to measurehemoglobin concentrations according to some embodiments.

FIG. 6 is a graph that illustrates relative absorbance of hemoglobin atvarious wavelengths, and minimum and maximum wavelengths utilized tomeasure hemoglobin concentrations according to some embodiments.

FIG. 7 is a flowchart that illustrates steps utilized to measurehemoglobin concentrations by utilizing an isosbestic wavelengthaccording to some embodiments.

FIG. 8 is a graph that illustrates relative absorbance of hemoglobin atvarious wavelengths, and utilization of an isosbestic wavelength as asignificant wavelength for both oxyhemoglobin and deoxyhemoglobinmaximum wavelengths according to some embodiments.

FIG. 9 is a flowchart that illustrates steps utilized to measurehemoglobin concentrations using two light sources and a single detectoraccording to some embodiments.

FIG. 10 is a flowchart that illustrates long-term monitoring and storageof hemoglobin concentrations and one or more physiological signals todetect patient conditions according to some embodiments.

FIG. 11 is a flowchart that illustrates dynamic monitoring and storageof hemoglobin concentrations and one or more physiological signals todetect patient conditions according to some embodiments.

DETAILED DESCRIPTION

FIG. 1 illustrates a patient P and a monitoring system 10 fornon-invasive monitoring of blood concentration levels (e.g., hemoglobin,oxyhemoglobin, deoxyhemoglobin, etc.) In the embodiment shown in FIG. 1,monitoring system 10 comprises a patient medical device 100 and/or 110,gateway 102, and remote monitoring center 106. In the embodiment shownin FIG. 1, patient medical device 100 is an adherent device thatattaches to the skin of the patient, and patient medical device 110 is aclip that fits over a patient's finger. In other embodiments, patientmedical device may include implantable devices, insertable devices,injectable devices, and/or wearable devices such as a Holter monitor(collectively referred to as a medical device). In each example, thepatient medical device utilizes optical components to monitor bloodconcentration levels of the patient. In some embodiments, patientmedical device 100 includes one or more additional sensors formonitoring one or more additional physiological parameters of thepatient, such as activity, orientation, cardiac activity, hydration,etc.

In the embodiment shown in FIG. 1, medical device 100 is adhered to thethorax T of patient P, which allows for the monitoring of additionalphysiological parameters, such as ECG, hydration, activity, etc. In manyembodiments, the device may adhere to one side of the patient, fromwhich side data can be collected. A benefit of utilizing an adherentdevice, implantable, injectable, and/or wearable device is that it maybe utilized to collect physiological data from the patient while thepatient goes about normal day-to-day activities outside of a hospitalsetting. A medical device clipped to a patient's finger, such as medicaldevice 110, is not worn throughout the day by a patient, but may beuseful in applications such as these due to the relative ease inapplying the clip to a patient's finger in order to take a reading. Thatis, rather than wearing the device for an extended period of time, apatient may periodically clip the device to the patient's finger for afew moments (e.g., seconds) in order to non-invasively measure a bloodconcentration level (e.g., oxy-Hb, deoxy-Hb), and then remove.

As discussed above, in some embodiments, the medical device may monitora number of physiological parameters associated with patient P,including optical signals utilized to determine blood concentrationlevels, electrocardiogram (ECG) signals utilized to detect rhythmabnormalities such as tachycardia and/or bradycardia as well as activitylevel data, posture, bio-impedance, etc. Analysis of one or more ofthese physiological parameters may be done locally by the medicaldevices 100 or 110, or remotely by gateway 102 and/or remote monitoringcenter 106 (or similar platform separate from the local medical device100). In one embodiment, gateway 102 is a stand-alone deviceinstalled—typically—in the patient's home. In other embodiments, gateway102 may be a patient device (such as a smartphone, tablet, or computer)capable of storing and executing one or more applications designed toprocess signals received from medical devices 100 and/or 110.Non-invasive monitoring of blood concentration levels relies on one ormore optical sensors positioned on the medical device to provide anexcitation source (e.g., light) to patient tissue and monitor theemission response (e.g., light emitted by the patient tissue as a resultof reflection, fluorescence, absorbance of the incident light). Forexample, in one embodiment one or more light sources associated with themedical device direct incident light to patient tissue. In addition, oneor more photodetectors associated with the medical device receives lightemitted from the patient at a particular emission wavelength associatedwith the photodetector (e.g., wavelengths of 590 nm). The photodetectorconverts the measured emission (i.e., optical signal) to an electricalsignal that is representative of the amplitude or strength of theemitted light. As discussed in more detail below, analysis of thedetected optical signal can be utilized to monitor blood concentrationlevels. In some embodiments, the analysis is performed locally by themedical device 100 or 110, while in other embodiments the monitoredoptical signal is transmitted to a gateway 102 or remote center 106 foranalysis to detect blood concentration levels.

In one embodiment, gateway 102 comprises components of the zLink™, asmall portable device similar to a cell phone that wirelessly transmitsinformation received from medical device 100 to remote monitoring center106. The gateway 102 may consist of multiple devices, which cancommunicate wired or wirelessly with remote center 106 in many ways, forexample with a connection 104 which may comprise an Internet connectionand/or with a cellular connection. Remote center 106 may comprise ahosted application for data analysis and storage that also includes awebsite, which enables secure access to physiological trends andclinical event information for interpretation and diagnosis. Remotecenter 106 may further or alternatively comprise a back-end operationwhere physiological data from adherent devices 100 or 110 are read byhuman experts to verify accuracy. Reports may then be generated atremote monitoring center 106 for communication to the patient'sphysician or care provider. As discussed above, in other embodimentsgateway 102 may be implemented with a user device such as a smartphone,tablet, or computer capable of storing and executing one or moreapplications capable of processing data received from medical devices100 and/or 110, as well as communicating the received data to remotemonitoring center 106.

In an exemplary embodiment, the monitoring system comprises adistributed processor system with at least one processing module (notshown) included as part of adherent device 100, at least one processor102P of gateway 102, and at least one processor 106P at remote center106, each of which processors can be in electronic communication withthe other processors. At least one processor 102P comprises a tangiblemedium 102T, and at least one processor 106P comprises a tangible medium106T. Remote processor 106P may comprise a backend server located at theremote center. Physiological parameters—including opticalsignals—monitored by medical device 100 may be analyzed by one or moreof the distributed processors included as part of medical device 100,gateway 102, and/or remote monitoring center 106.

FIGS. 2A-2C are perspective views of an adherent monitoring deviceaccording to some embodiments. Adherent devices are adhered to the skinof a patient, and include one or more sensors utilized to monitorphysiological parameters of the patient. Adherent devices areoften-times utilized for long-term monitoring of ambulatory patients,allowing physiological parameters of the patient to be monitored over aperiod of time (e.g., days, weeks, months). Adherent devices thereforeallow for both long-term monitoring of patients with chronic conditions(e.g., anemia) as well as monitoring and detection of acute incidences(e.g., carbon monoxide poisoning). This is in contrast with typicalblood tests, which require blood be drawn by a lab and therefore do notallow for either long-term monitoring or detection of acute conditions.

The adherent device 200 illustrated in FIG. 2A illustrates therelatively low profile of adherent devices, which allows patients towear the devices comfortably over a long period of time.

In the embodiment shown in FIG. 2B, a bottom surface 202 of adherentdevice 200 is shown, which includes a plurality of electrodes 204 a-204d, at least one light emitter 206, and two photodetectors 208 a, 208 b.Electrodes 204 a-204 d are utilized to monitor electrical activityassociated with the patient, including monitoring electrocardiogram(ECG) information and bio-impedance. The at least one light emitter 206is utilized to generate an excitation signal (e.g., incident light)provided incident to patient tissue. Light provided by emitter 206 maybe comprised of a plurality of wavelengths, including visible light,ultraviolet light (shorter wavelengths than visible light), and infraredlight (longer wavelengths than visible light). In other embodiments,light provided by emitter 206 may be comprised of one or more selectedwavelengths. Depending on the particular aspect/component of blood to bemonitored (e.g., hemoglobin, oxyhemoglobin, deoxyhemoglobin,glycosylated hemoglobin A1c (HbA1c), hematocrit levels, etc.), differentwavelengths of light may be selected in order to generate a particularemission response, which refers to how the incident light at aparticular wavelength interacts with blood components via reflectance,absorbance, fluorescence, etc., which is represented by the lightemitted from the patient. For example, hemoglobin is defined by anemission response to incident light provided at a particular wavelength.

In addition, the embodiment shown in FIG. 2B, the bottom surface 202 ofadherent device 200 includes two or more photodetectors 208 a, 208 b. Inthis embodiment, each photodetector is configured to detect light at aparticular emission wavelength. The wavelength selected is based on theemission response or morphology of the blood component being analyzed(e.g., hemoglobin, hematocrit, platelets, etc.). In a lab environment,the entire spectral response (e.g., all wavelengths) may be measured andanalyzed. This is cost prohibitive though in an adherent device. Insteadof monitoring all wavelengths, the embodiment shown in FIG. 2B selectstwo or more wavelengths to monitor. The wavelengths are selected basedon the particular blood component being analyzed, and are selected tocorrelate with at least one maximum and at least one minimum of theemission response. Alternatively, the emission wavelength could beselected to reflect significant wavelength from the absorbance spectraof Hb. For example, hemoglobin is defined by a spectral response thatincludes a maximum at a wavelength of approximately 575 nm, and aminimum at a wavelength of approximately 560 nm. In this example,photodetector 208 a may be configured to monitor an attribute (e.g.,amplitude) of the emission response provided at 575 nm, andphotodetector 208 b may be configured to monitor an attribute (e.g.,amplitude) of the emission response provided at 560 nm.

Based on the measured attribute of emitted light at select wavelengths,a ratio of the measured attributes is calculated, wherein the ratioprovides a measure of the blood concentration component. A benefit ofutilizing a ratio is that the measure is relatively immune to noise andexternal factors such as change in ambient light intensity, moleculeconcentrations, artifacts, light source instability, detectorinstability, and/or changes in placement of the sensor. For example, ameasurement taken during the night in which little or no external lightis available may provide an amplitude that is much lower than theamplitude measured if the patient is outside in the sun—in which lightfrom the sun increases the measured amplitude at both the minimum andthe maximum.

Although in the embodiment shown in FIG. 2B, a single emitter 206 isshown along with a pair of detectors 208 a and 208 b, in otherembodiment a plurality of emitters may be utilized along with more thantwo detectors. In addition, although each emitter and detector isillustrated as a separate entity, in some embodiments the functions ofan emitter and detector are included in a single device. Therefore, onone embodiment light source 206 may also include a photodetector 208.Photodetectors may be implemented with well-known imaging sensors suchas CCD or CMOS image sensors.

In contrast with the embodiment shown in FIG. 2B, in which the number ofdetectors 208 was greater than the number of emitters 206, in otherembodiments the number of emitters 206 may be greater than the number ofdetectors 208. For example, in the embodiment shown in FIG. 2C, ratherthan utilize a single light source or emitter and two or more detectors,adherent device 210 includes a pair of emitters 212 a and 212 b and asingle photodetector 214. In this embodiment, each light source oremitter 212 a and 212 b provides incident light at a unique wavelength.Photodetector 214 monitors emissions at a single wavelength, selected tocorrespond with an emission response associated with first excitationwavelength, and an emission response associated with the secondexcitation wavelength.

In some embodiments, emitters 212 a and 212 b are controlled to generateincident light mutually exclusive of one another (e.g., one at a time).This allows detector 214 to measure the emission response associatedwith the first excitation wavelength and the emission responseassociated with the second excitation wavelength, separately. Forexample, in one embodiment emitter 212 a is activated to provideincident light at a first wavelength. Photodetector 214 measures anattribute (e.g., amplitude) relating to the emission response at a givenemission wavelength. Subsequently, emitter 212 a is deactivated andemitter 212 b is activated to provide incident light at a secondwavelength. Photodetector 214 measures the attribute (e.g., amplitude)relating to the emission response at the same given emission wavelength.The ratio of the measured amplitudes is utilized to measure a bloodconcentration component (e.g., hemoglobin).

In other embodiments, more than two light sources (e.g., emitters) maybe utilized to provide incident light at more than two uniquewavelengths. In addition, more than a single photodetector may beutilized in order to measure attributes of the emission response at aplurality of emission wavelengths. Similarly, although a pair ofemitters 212 a and 212 b and a single photodetector 214 are utilized inFIG. 2C, in other embodiments more than two emitters may be utilizedalong with a plurality of photodetectors. In addition, although eachemitter and photodetector is illustrated as a separate entity, in someembodiments the functions of an emitter and photodetector are includedin a single element.

FIG. 3 is a perspective view of an insertable monitoring device 300according to some embodiments. In contrast with an adherent device,which is secured to the skin of a patient, insertable monitoring devices300 are inserted subcutaneously. Insertable device 300 includes at leastfirst and second electrodes 302 a and 302 b, at least one emitter 304and at least one photodetector 308. As discussed above, in order togenerate the desired ratio, at least two emitters 304 are required incombination with at least one detector 308, or at least twophotodetectors 308 are required in combination with at least emitter304. For example, in one embodiment insertable monitoring device 300utilizes first and second photodetectors, each measuring attributes atunique emission wavelengths and at least one emitter providing light ata desired excitation wavelength. In this embodiment, the emissionwavelengths selected for first and second photodetectors 308 is based onthe particular blood component being analyzed, and are selected tocorrelate with at least one maximum and at least one minimum of theemission response of the component being monitored. For example,oxyhemoglobin is defined by an emission response that includes a maximumat a wavelength of approximately 575 nm, and a minimum at a wavelengthof approximately 560 nm. In one embodiment, first photodetector 308 maybe configured to monitor the amplitude of light provided at 575 nm, andsecond photodetector 308 may be configured to monitor the amplitude oflight provided at 560 nm.

Likewise, in another embodiment insertable monitoring device 300utilizes two or more emitters (i.e., a second emitter in addition toemitter 304) and at least one photodetector 308. In this embodiment, afirst emitter provides light at a first excitation wavelength and secondemitter provides light at a second excitation wavelength. The first andsecond emitters are controlled so that incident light is provided atdifferent times. For example, the first emitter may generate incidentlight for a first period of time, and the second emitter may generateincident light for a second period of time following the first period oftime. Photodetector 308 measures one or more attributes associated withthe emission response at each of the excitation wavelengths. A ratio iscalculated based on the measured attributes and utilized to determinethe desired ratio utilized to determine the blood componentconcentration. A benefit of utilizing ratios is that placement of theinsertable device may have an impact on the magnitude of the attributesmeasured. For example, placement over a vein may increase the absolutevalue of measured attributes. By utilizing a ratio, variation inabsolute values based on placement is mitigated.

FIG. 4 is a block diagram illustrating components utilized to monitoroptical signals and processing optical signals according to someembodiments.

Medical device 400 includes at least one light source 402, at least onedetector 404, filter/amplifier 406, processor/microcontroller 408,memory 410, and communication/output 412. As described above, medicaldevice 400 may be adhered to the patient's skin, clipped onto apatient's finger, attached via an arm cuff, inserted subcutaneously, orimplanted within the patient. Light source 402 emits light that isprovided incident to the patient's tissue, referred to herein as“excitation”. In some embodiments, excitation may be provided at aplurality of wavelengths or at a selected wavelength. For example, thewavelength of the emitted light may be selected based on the bloodcomponent (e.g., particular protein) to be analyzed, wherein differentwavelengths of light interact differently with particular proteins. Insome embodiments, light source 402 includes a plurality of light sourceseach capable of emitting at a particular unique wavelength.

Light from light source 402 interacts with patient tissue 414 or patientfluid, protein or photo-active molecule. The interaction is a result ofone or more processes, including autofluorescence, absorption,transmittance and reflectance that results in the emission of light fromthe tissue, referred to as the emission response. The emission responseis detected by the one or more photodetectors 404, which may be placeadjacent to the light source 402 (as shown in FIGS. 2B, 2C and 3) or onthe opposite side of patient tissue as is common in pulse oximeters. Insome embodiments, photodetector 404 may utilize well-known opticalsensors, such as complimentary metal-oxide-semiconductor (CMOS) sensoror a charge-coupled device (CCD) sensor. Each of the one or morephotodetectors 404 is configured to detect light at a particularemission wavelength. For embodiments in which a plurality of emissionwavelengths are monitored, a plurality of photodetectors 404 arerequired, each configured to monitor one of the desired emissionwavelengths. The emission wavelengths monitored by the one or morephotodetectors 404 are selected based on the particular blood componentbeing monitored. For example, the emission response morphology (i.e.,amplitude of the emission response across the entire wavelengthspectrum) depends on how light interacts with the blood component beingmonitored, with emission responses for each blood component providingdifferent emission response morphology. In particular, emissionwavelengths monitored by the one or more photodetectors are selected tocorrespond with maximum and/or minimum values associated with theemission response spectrum being monitored, or with wavelength(s) ofsignificance on the emission spectrum.

The one or more photodetectors convert the monitored optical signal(i.e., the emission response) to an electrical signal representative ofthe amplitude of the emission wavelength being monitored.Filter/amplifier 406 filters and amplifies the signal to provide a cleansignal to processor/microcontroller 408.

Processor/microcontroller 408 operates in conjunction with memory 410and communication output 412. In some embodiments,processor/microcontroller 408 provides the measured emission responsesignals monitored by the photodetectors to an intermediate gateway 102and/or remote monitoring center 106 (shown in FIG. 1) for subsequentprocessing. In other embodiments, processor/microcontroller 408 executesinstructions locally to perform analysis on the monitored emissionresponse. This may include calculating ratios associated with two ormore monitored emission responses, calculating blood componentconcentrations based on the calculated ratios, comparing the ratiosand/or blood component concentrations to threshold values, and/orstoring calculated ratios and/or blood component concentrations tomemory 410. Results of any analysis performed locally byprocessor/microcontroller may then be communicated to intermediatedevice 102, gateway 106, or provided as an alert to the patient (e.g.,audio alert).

FIG. 5 is a flowchart that illustrates steps utilized to measurehemoglobin concentrations according to some embodiments. Reference ismade to FIG. 6, which is a graph that illustrates relative absorbance ofoxy-Hb (line 600) and deoxy-Hb (line 602) at various wavelengths, andminimum and maximum wavelengths utilized to measure hemoglobinconcentrations according to some embodiments. The change in relativeabsorbance is a result of changes in the molecular structure when anoxygen molecule is attached to the hemoglobin versus when no oxygenmolecule is attached. A typical pulse oximeter utilizes a wavelength inwhich the relative absorption of oxy-Hb and deoxy-Hb differsignificantly and utilizes the measured amplitude to determine theconcentration of oxy-Hb to deoxy-Hb. For example, at a wavelength ofapproximately 660 nm (far right of FIG. 6), the relative absorbancevaries significantly between oxy-Hb and deoxy-Hb. Measuring theamplitude of light transmitted at 660 nm and measuring the amplitude oftransmitted light allows for a determination to be made regardingconcentration of oxy-Hb and/or deoxy-Hb. However, as an absolutemeasurement, this measurement is highly susceptible to noise and outsideinfluence. For example, a change in ambient light levels will have aneffect on the measured amplitude, resulting in errors in themeasurement. In contrast, the present invention utilizes minimums andmaximums in the known emission response to generate one or more ratios,as discussed in more detail below.

At step 500, one or more light sources are utilized to illuminatepatient tissue at one or more excitation wavelengths. In one embodiment,the light source is provided at a wavelength selected based on the bloodconcentration component to be measured. For example, typically awavelength is selected in the ultraviolet (UV), visible, or infrared(IR) spectrums in order to generate an absorbance, reflectance,transmittance and/or fluorescence response (i.e., emission response)having the desired spectral morphology. In the embodiment shown in FIGS.5 and 6, light is provided at a single excitation wavelength (e.g., redvisible light, infrared light), but in other embodiments may be providedat a plurality of wavelengths (e.g., visible white light).

In response to the excitation provided by the light source, an emissionresponse is generated that is a function of, at least in part, theconcentration of oxy-Hb and deoxy-Hb in the patient's tissue. A fullspectrum sweep of each of the wavelengths shown in FIG. 6 andmeasurement of the resulting emission response is one method ofdetermining the concentration of oxy-Hb and deoxy-Hb, but as discussedabove this is prohibitive in terms of computational and battery powerrequirement. To overcome the cost of a full spectrum wavelength sweep tomeasure the co ncentration levels of various blood components,wavelength measurements are limited to monitoring two emissionwavelengths.

At step 502, first and second photodetectors measure emission at a firstwavelength λ₁ and a second wavelength λ₂, respectively. The firstemission wavelength λ₁ is selected to correspond with a known maximum ofthe emission response. For example, in the embodiment shown in FIG. 6,the maximum associated with oxy-Hb occurs at approximately λ₁ (e.g.,wavelength of 578 nm). The second emission wavelength λ₂ is selected tocorrespond with a known minimum of the oxy-Hb emission response. Forexample, in the embodiment shown in FIG. 6, a minimum associated withoxyhemoglobin occurs at approximately any wavelength greater than 620 nm(e.g., 640 nm is selected in this embodiment). If deoxy-Hb is to bemonitored, then emission wavelengths are selected that correspond withmaximum and minimum values of the deoxy-Hb emission response. Forexample, an emission wavelength λ₃ corresponding with a maximum of thedeoxy-Hb emission response is selected (e.g., wavelength ofapproximately 555 nm) and a second emission wavelength λ₄ correspondingwith a minimum of the deoxy-Hb emission response is selected (e.g.,wavelength greater than approximately 640 nm, 650 utilized in thisembodiment). In some embodiments, the minimum value associated withoxy-Hb and deoxy-Hb may utilize the same emission wavelength (e.g.,wavelength of 640 nm).

The measurement taken at step 502 is a measurement of an attribute(e.g., intensity, amplitude, phase, etc.) of the emission response. Ingeneral, the photodetector responsible for measuring the attribute at aparticular emission wavelength converts the detected light into anelectrical signal representative of the measured attribute. In theembodiment shown in FIG. 6, the measured amplitude is analyzed based onrelative absorbance spectrum, but may take into account one or moreother processes that affect emissions of light from the tissue inresponse to the incident light. In general, the concentration of bloodat any particular time is a combination of oxy-Hb and deoxy-Hb, suchthat the amplitude measured is a combination of absorbance resultingfrom the oxy-Hb concentration and the deoxy-Hb concentration. At theminimum wavelength selected (e.g., λ₂), both oxy-Hb and deoxy-Hb exhibita relatively low absorbance. In contrast, a large difference in relativeabsorbance of oxy-Hb and deoxy-Hb is exhibited at the maximum wavelengthselected (e.g., λ₁). This difference in relative absorbance is requiredin order to utilize the measured amplitudes to determine the relativeconcentration levels of oxy-Hb and deoxy-Hb. For example, the amplitudeof the emission response at wavelength λ₁ will decrease as theconcentration of oxy-Hb concentration increases due to the difference inrelative absorbance of oxy-Hb to deoxy-Hb at this wavelength, withoxy-Hb exhibiting greater relative absorbance. However, the emissionresponse at wavelength λ₁ will also decrease in response to ambientconditions changing, such as the patient walking from an outdoorenvironment to an indoor environment, which cannot be known simply bymeasuring the raw amplitude at a particular wavelength, resulting inerroneous determinations of oxy-Hb. To address this change in absoluteamplitudes in response to external conditions (e.g., ambient lightconditions), one or more ratios are utilized. Other factors that couldintroduce an error to the absolute raw amplitude include body motion,muscle flexing, circulatory perfusion, movement of the incident lightrelative to the patient tissue, etc.

At step 504, one or more ratios R are calculated based on the emissionsmeasured at the first and second wavelengths λ₁ and λ₂ (e.g., R₁=λ₁/λ₂).The calculated ratio may be calculated on the medical device 100, 110(shown in FIG. 1), or may be measured at an intermediate device 102 (asshown in FIG. 1) or remotely at a remote monitoring center 106 (as shownin FIG. 1). A benefit of utilizing a ratio R as opposed to an absolutemeasure at a particular emission wavelength is that use of the ratio Rdecreases the effect of noise on the measured blood concentration. Forexample, the effect of changes in ambient light (which also interactswith the patient's tissue) are negated through the use of a ratio ofmaximum and minimum values. For example, in the embodiment shown in FIG.6 in which oxy-Hb is being monitored, the ratio R may be calculatedbased on the amplitude measured at wavelengths λ₁ divided by theamplitude measured at wavelength λ₂. A change in ambient light thatdecreases the amplitude of the emission response at wavelength λ₁similarly and proportionally decreases the amplitude of the emissionresponse at wavelength λ₂.

In one embodiment, the ratio R is defined as the amplitude measured atwavelength λ₁ divided by the amplitude measured at wavelength λ₂ (e.g.,R=A_(λ1)/A_(λ2)). As oxy-Hb concentrations increase, the amplitudemeasured at wavelength λ₁ decreases in response to the higher absorptionof increasing oxy-Hb concentrations. The amplitude measured atwavelength λ₂ may increase slightly as deoxy-Hb absorbs more light atwavelength λ₂, however, the relative absorbance of both oxy-Hb ordeoxy-Hb are fairly low at wavelength λ₂ and therefore the amplitudemeasured at wavelength λ₂ will remain relatively unchanged. The netresult is a decrease in the ratio R in response to increasing oxy-Hbconcentrations. Furthermore, no substantial change in the ratio Rresults from a change in ambient light. For example, if a patient movesfrom outdoors (e.g., sunny environment) to indoors, the correspondingdecrease in measured amplitudes is relatively the same at wavelengths λ₁and λ₂, resulting in the ratio remaining relatively constant in light ofchanging ambient conditions.

In other embodiments, various other ratios R may be calculated based onthe emission wavelengths measured. For example, the ratio may be definedas the amplitude measured at wavelength λ₃ (maximum) and wavelength λ₄(minimum), which provides information on deoxy-Hb concentration levels.In other embodiments, the ratio may be defined as the amplitude measuredat wavelength λ₁ (oxy-Hb maximum) and wavelength λ₃ (deoxy-Hb maximum),to provide a ratio of oxy-Hb concentration levels to deoxy-Hbconcentration levels.

At step 506, the calculated ratio R is utilized to determine the bloodcomponent concentration level (e.g., oxy-Hb concentration, deoxy-Hbconcentration, etc.). In one embodiment, the concentration levels may becorrelated with various ratios R. For example, the medical device (orremote monitoring center) may include a stored table that correlatesmeasured ratios with concentration levels. In other embodiments, aplurality of ratios may be utilized to determine concentration levels.For example, in the embodiment shown in FIG. 6, a first ratio R₁ may becalculated based on the maximum/minimum associated with oxy-Hb and asecond ratio R₂ may be calculated based on maximum/minimum associatedwith deoxy-Hb. The plurality of ratios may be utilized alone or inconjunction with one another to determine concentration levels. Forexample, the combination of ratios R₁ and R₂ may be utilized todetermine the total concentration of hemoglobin (e.g., combination ofoxy-Hb and deoxy-Hb).

In one embodiment, determining one or more blood component concentrationlevels is performed locally by the medical device (e.g., adherent device100, 200 shown in FIGS. 1 and 2A-2C, monitoring clip 110 shown in FIG.1, insertable device 300 shown in FIG. 3, etc.). In other embodiment,measured amplitude and/or ratios are communicated to an intermediatedevice and/or remote monitoring center and determination ofconcentration levels is performed by the intermediate and/or remotemonitoring center.

At step 508, the determined concentration level is stored and/oranalyzed to detect patient conditions. For example, in one embodimentthe determined concentration level (e.g., hemoglobin concentrationlevel) is compared to a threshold level to detect conditions such asanemia. In some embodiments, the threshold level is an absolute value,while in other embodiments the threshold level is initialized withrespect to the patient. For example, to calculate an initialized value,a concentration level may be determined at an initial period (viaoptical monitoring or via blood test). Having determined an initialvalue, the threshold level is determined based on the initial value andis utilized to detect conditions such as anemia.

In one embodiment, storage of the concentration level and/or comparisonof the concentration level to a threshold level to detect a patientcondition is done locally on the medical device (e.g., adherent device,insertable device, etc.). In other embodiments, storage of theconcentration level and/or comparison of the concentration level to athreshold level to detect a patient condition is done remotely at anintermediate device and/or remote monitoring center. In response to adetected condition, such as anemia and/or other hemoglobin relatedconditions, an alert or alarm may be generated and communicated to thepatient and/or a monitoring party (e.g., physician, hospital, etc.).

A benefit of the method described in FIGS. 5 and 6 is the ability toprovide long-term monitoring of blood component concentration levels. Incontrast with typical lab tests, which monitor concentration levels atthe instant in time in which blood is drawn, the present inventionallows concentration levels to be monitored for long periods of time(e.g., days, weeks). Benefits of long-term monitoring include theability to detect acute conditions throughout the monitoring period andto alert the patient of the acute condition to reduce the amount of timeit takes the patient to receive a diagnosis. Benefits of long-termmonitoring further include the ability to average concentration levelsover a period of time to account for variations in blood componentconcentration levels (which vary on short time-tables related to patientheart-beat, as well as longer time tables in response to patientcondition). In addition, long-term monitoring allows concentrationtrends to be detected and utilized to determine whether a condition isimproving or worsening. For example, long-term monitoring can beutilized to monitor the efficacy of treatment, and/or monitorprogression or worsening of a condition.

FIG. 7 is a flowchart that illustrates steps utilized to measurehemoglobin concentrations by utilizing an isosbestic wavelengthaccording to some embodiments. FIG. 7 is a graph that illustratesrelative absorbance of hemoglobin at various wavelengths, andutilization of an isosbestic wavelength as a minimum for both oxy-Hb anddeoxy-Hb maximum wavelengths according to some embodiments.

In general, the embodiment shown in FIGS. 7 and 8 is similar to thatdescribed with respect to FIGS. 5 and 6. The main difference is inselection of the emission wavelength minima (e.g., the emissionwavelength corresponding with an emission response minimum). In contrastwith the embodiments shown in FIGS. 5 and 6, in the embodiment shown inFIGS. 7 and 8 the emission wavelength minimum is selected at anisosbestic point that represents a point at which the total absorbanceof a sample does not change during a chemical reaction or a physicalchange of the sample. For example, as illustrated in FIG. 8, anisosbestic point exists at an emission wavelength λ₅ (e.g., wavelengthof approximately 510 nm). At the isosbestic point, the emission responseof both oxyhemoglobin (line 800) and deoxyhemoglobin (line 802) areequal to one another. By utilizing an isosbestic point as the emissionwavelength minimum, ratios can be calculated for measuring bothoxyhemoglobin and deoxyhemoglobin via monitoring of only three emissionwavelengths (rather than the four utilized in the embodiment shown inFIGS. 5 and 6).

At step 700, one or more light sources are utilized to illuminate tissueat one or more excitation wavelengths. As discussed above, theexcitation wavelength may be selected based on the blood component to bemeasured (i.e., the excitation wavelength is selected to generate anemission response having the desired morphology). For monitoring bloodcomponent concentrations, typically the excitation wavelength utilizedis in the visible red spectrum or infrared spectrum. In otherembodiments, the light source is provided at a plurality of wavelengths(e.g., white light).

At step 702, one or more photodetectors are utilized to measureemissions at a first wavelength λ₅, a second wavelength λ₆, and a thirdwavelength λ₇. In some embodiments, only two emission wavelengths needto be monitored in order to measure either oxy-Hb or deoxy-Hb, but inthis example three emission wavelengths are monitored and utilized tomeasure two blood component concentrations. As discussed above,measuring the entire emission response (e.g., measuring at allwavelengths) is prohibitive. However, information about the Oxy-Hb bloodcomponent concentration can be determined by measuring the emissionresponse at isosbestic wavelength λ₅ and a second wavelength λ₆. Thefirst emission wavelength λ₅ is selected to correspond with asignificant wavelength of the emission response that also correspondswith an isosbestic point between the oxy-Hb emission response and thedeoxy-Hb emission response. For example, in the embodiment shown in FIG.8, an isosbestic point exists at an emission wavelength of approximately510 nm. In addition to an isosbestic point, second and third emissionwavelengths λ₆ and λ₇ are selected to correspond with maximumsassociated with the oxy-Hb emission response and the deoxy-Hb emissionresponse. In the embodiment shown in FIG. 8, the maximum emissionresponse associated with oxyhemoglobin occurs at wavelength λ₆ (e.g.,wavelength of approximately 578 nm, or alternatively a local maximum at540 nm may be utilized) and the maximum emission response associatedwith deoxyhemoglobin occurs at wavelength λ₇ (e.g., wavelength ofapproximately 555 nm).

The measurement taken at step 702 is a measurement of theintensity/amplitude of the emission response. As discussed above, thephotodetector responsible for measuring the amplitude at a particularemission wavelength converts the detected light into an electricalsignal representative of the measured amplitude. In the embodiment shownin FIG. 7, the measured amplitude is a measure of the relativeabsorbance, but may be related to one or more other processes thatresults in the emission of light from the tissue in response to theincident light.

At step 704, one or more ratios R are calculated based on the emissionsmeasured at the first, second, and third wavelengths λ₅, λ₆ and λ₇. Afirst calculated ratio R₁ is calculated based on first and secondwavelengths λ₅ and λ₆, and provides information on oxy-Hbconcentrations. A second calculated ratio R₂ is calculated based onfirst and third wavelengths λ₅ and λ₇, and provides information ondeoxy-Hb concentrations. As discussed above, utilizing an isosbesticpoint allows ratios to be calculated for both oxyhemoglobin anddeoxyhemoglobin concentrations via monitoring of three emissionwavelengths, rather than four.

At step 706, the calculated ratios R₁ and R₂ is utilized to determinetwo or more concentration levels (e.g., oxy-Hb concentration, deoxy-Hbconcentration, etc.). In other embodiments, a plurality of ratios may beutilized to determine concentration levels. For example, in theembodiment shown in FIG. 8, a first ratio R₁ may be calculated based onthe maximum/minimum associated with oxy-Hb and a second ratio R₂ may becalculated based on maximum/minimum associated with deoxy-Hb. In thisway, measurement of the first and second ratios allows for thediscrimination of the two components of hemoglobin and their relativevalues. The plurality of ratios may be utilized alone or in conjunctionwith one another to determine concentration levels. For example, thecombination of ratio R₁ and R₂ may be utilized to determine the totalconcentration of hemoglobin (e.g., combination of oxyhemnoglobin anddeoxyhemoglobin).

In one embodiment, determining one or more blood component concentrationlevels is performed locally by the medical device (e.g., adherentdevice, insertable device, etc.). In other embodiment, measuredamplitude and/or ratios are communicated to an intermediate deviceand/or remote monitoring center and determination of concentrationlevels is performed by the intermediate and/or remote monitoring center.

At step 708, the determined concentration level is stored and/oranalyzed to detect patient conditions. For example, in one embodimentthe determined concentration level (e.g., hemoglobin concentrationlevel) is compared to a threshold level to detect conditions such asanemia. In some embodiments, the threshold level is an absolute value,while in other embodiments the threshold level is initialized withrespect to the patient. For example, to calculate an initialized value,a concentration level may be determined at an initial period (viaoptical monitoring or via blood test). Having determined an initialvalue, the threshold level is determined based on the initial value andis utilized to detect conditions such as anemia.

As discussed above with respect to FIGS. 5 and 6, in some embodiments,storage of the concentration level and/or comparison of theconcentration level to a threshold level to detect a patient conditionis done locally on the medical device (e.g., adherent device, insertabledevice, etc.). In other embodiments, storage of the concentration leveland/or comparison of the concentration level to a threshold level todetect a patient condition is done remotely at an intermediate deviceand/or remote monitoring center. In response to a detected condition,such as anemia and/or other hemoglobin related conditions, an alert oralarm may be generated and communicated to the patient and/or amonitoring party (e.g., physician, hospital, etc.).

FIG. 9 is a flowchart that illustrates steps utilized to measurehemoglobin concentrations using two light sources and a single detectoraccording to some embodiments, such as the embodiment shown in FIG. 2C.

At step 900, a first light source is utilized to illuminate patienttissue at a first excitation wavelength. As discussed above, theexcitation wavelength may be selected based on the blood component to bemeasured (i.e., the excitation wavelength is selected to generate anemission response having the desired morphology). For monitoring bloodcomponent concentrations, typically the excitation wavelength utilizedis in the ultraviolet, visible or infrared spectrum. While the firstlight source is turned ON or emitting light, the second light sourceremains OFF, such that only a single light source is emitting light at agiven time.

At step 902, at least one photodetector is utilized to measure emissionsin response to the first excitation wavelength. In contrast withembodiments described with respect to FIGS. 5-8, in some embodimentsonly a single emission wavelength is monitored. The emission wavelengthutilized by the at least one photodetector is selected to correspondwith a known minimum and/or maximum of the emission response associatedwith the excitation wavelength of the first light source. As discussedabove, the emission response may be a result of one or more of tissueabsorbance, fluorescence, reflectance, etc., and the emission responsemorphology (e.g., measured amplitude at all wavelengths) is a result ofthe excitation wavelength provided by the first light source. Selectinga minimum/maximum along the emission response allows informationregarding the blood component being analyzed to be determined withoutrequiring monitoring the entire spectrum of emission wavelengths.

As discussed above, the measurement taken at step 902 is a measurementof the intensity/amplitude of the emission response to the firstexcitation wavelength. The photodetector responsible for measuring theamplitude at a particular emission wavelength converts the detectedlight into an electrical signal representative of the measuredamplitude.

At step 904, a second light source is utilized to illuminate patienttissue at a second excitation wavelength. As discussed above, theexcitation wavelength may be selected based on the blood component to bemeasured (i.e., the excitation wavelength is selected to generate anemission response having the desired morphology). For monitoring bloodcomponent concentrations, typically the excitation wavelength utilizedis in the ultraviolet, visible or infrared spectrum. However, both thefirst excitation wavelength and second excitation wavelengths must beunique in order to generate unique emission responses. With the secondlight source ON, the first light source is turned OFF, such that only asingle light source is emitting light at a given time.

The excitation wavelength of the second light source is selected basedon the blood component to be measured, such that the emission responseprovides the desired morphology. However, whereas the first excitationwavelength was selected to generate an emission response having amaximum at the monitored emission wavelength, the second excitationwavelength is selected to generate an emission response providingsomething other than a maximum at the monitored emission wavelength,preferably a minimum, based on the blood component concentration to bemeasured.

At step 906, the at least one photodetector is utilized to measureemissions in response to the second excitation wavelength. In thisembodiment, because it is the excitation wavelength that is beingmodified—not the emission or monitored wavelength—it is important thatthe emission wavelength monitored by the at least one photodetector beselected to correspond with a maximum associated with the firstexcitation wavelength and a minimum or value relatively close to aminimum at the second excitation wavelength. In other embodiments, asecond photodetector may be utilized that measures emissions at a secondwavelength. However, for purposes of the embodiment shown in FIG. 8,only a single emission wavelength is measured.

At step 908, a ratio R is calculated based on the amplitude measured atthe first emission wavelength measured in response to first excitationwavelength and the amplitude measured at the first emission wavelengthin response to the second excitation wavelength. As discussed above, theratio represents the relationship between the amplitude measured withrespect to the maximum of the emission response and the amplitudemeasured with respect to the minimum of the emission response. Utilizingthis type of ratio allows external effects such as ambient light andnoise to be minimized and allows for accurate determination of bloodcomponent concentration levels without requiring monitoring of theentire spectrum of emission wavelengths.

FIG. 10 is a flowchart that illustrates long-term (e.g., chronic)monitoring and storage of hemoglobin concentrations and one or morephysiological signals to detect patient conditions.

At step 1000, a plurality of ratios are measured based on first andsecond amplitudes measured by one or more photodetectors over a firstmonitoring period (e.g., initialization period). A single light sourcemay be utilized along with multiple photodetectors associated withmultiple emission wavelengths, or a plurality of light sources may beutilized at two or more excitation wavelengths, along with one or morephotodetectors associated with one or more emission wavelengths. Ingeneral, at least one of the emission wavelengths is selected tocorrespond with a maximum of the emission response and at least one ofthe emission wavelengths is selected to correspond with a minimum of theemission response. This may be accomplished by selecting by properlyselecting the emission wavelength(s) and/or properly selecting theexcitation wavelength(s).

The initialization period requires a period of time long enough todetermine a baseline of the blood concentration value to be monitored.This may mean several minutes of monitoring, or several days ofmonitoring. A plurality of ratio measurements are taken during themonitoring period, allowing for averages and deviations associated withthe blood concentration value to be monitored. A benefit of utilizing aninitialization period, is measurements may vary from patient to patientbased on factors such as device placement—including general placement aswell as factors such as placement adjacent to a blood vessel—body typeof the patient, skin color, etc. Each of these factors may modify howlight interacts with the patient and the resultant emission responsefrom the patient.

In one embodiment, a plurality of unique ratios are collected in orderto monitor different blood concentration levels (e.g., oxyhemoglobin,deoxyhemoglobin, etc.). For example, a first unique ratio may be relatedto oxy-Hb levels, and at step 1000 a plurality of measurements are takenduring the first monitoring period with respect to the first uniqueratio. A second unique ratio may be related to deoxy-Hb levels, and atstep 1000 a plurality of measurements may be taken during the firstmonitoring period with respect to the second unique ratio.

At step 1002, for each unique ratio monitored, the plurality of ratioscorresponding with each unique ratio measured during the firstmonitoring period are averaged to develop a personalized ratio for thepatient. For example, a plurality of ratios associated withoxyhemoglobin concentration levels taken during the initializationperiod are averaged utilized to generate a baseline or initial ratiorepresenting the average oxyhemoglobin level of the patient. Thepersonalized ratio may represent a true averaging of the oxyhemoglobinlevels, a mean of the monitored ratios, or other statistical toolsutilized to determine a personalized ratio value or values.

At step 1004, the personalized ratio is utilized to set alarm/warningthresholds. In one embodiment, the threshold may be calculated at apredefined magnitude above and/or below the personalized ratio. Forexample, a personalized ratio related to oxy-Hb concentration (e.g.,oxygenated blood) may result in a threshold being set at fixed amountsabove and below the personalized ratio, creating a monitoring envelopearound the personalized ratio. In other embodiments, rather than apredetermined or fixed threshold above and/or below the personalizedratio, the envelope is defined by statistical tools such as standarddeviation. In other embodiment, the threshold is defined by a percentagechange in the personalized ratio, and in other embodiments may bedefined by a rate of deviation from the personalized ratio (e.g.,warning threshold reached if oxy-Hb levels change rapidly from apersonalized ratio). For each personalized ratio monitored, anindividual monitoring envelope may be created.

At step 1006, one or more ratios are monitored and compared to thealarm/warning thresholds to detect patient conditions. The one or moreratios may be individual measurements, or may be based on averaging aswell. For example, if ratio related to hemoglobin concentrations fallbelow a threshold value, this is an indication that the person may beanemic or experiencing blood loss, and requires medical attention. Inother embodiments, the ratio may be monitored for changes from aninitial value (e.g., percentage change), rate of change, etc.

At step 1008, an alert is generated in response to the monitored ratioexceeding or falling below one or more of the thresholds. In someembodiments, when a threshold is crossed, this triggers additionalmeasurements in order to confirm the accuracy of the result. This mayinclude increasing the frequency at which readings are taken, or simplycontinuing to monitor to ensure that the measured ratios are accurate.

The alert may be provided to the patient in the form of an audio orvisual alert. The alert may also be communicated to the intermediategateway 102 or remote monitoring center 106 (shown in FIG. 1). The alertmay be provided to a physician or expert for analysis and confirmationof the detected patient condition.

One of the benefits of the embodiment described with respect to FIG. 10,in combination with adherent and/or insertable devices is that theyallow for long-term monitoring of trends in blood concentration levels.In particular, the utilization of ratios minimizes the effect ofexternal influences and noise (such as changing ambient lightconditions, etc.), and initialization of the ratio to an average valuemonitored over an initial monitoring period allows the ratios to bepersonalized for each patient (to account for differences in thephysiology of each patient).

FIG. 11 is a flowchart that illustrates dynamic monitoring and storageof hemoglobin concentrations and one or more physiological signals todetect patient conditions. In this embodiment, one or more physiologicalparameters are measured and utilized to determine a patient state thattriggers measurement of one or more ratios related to bloodconcentration levels.

At step 1100, one or more physiological parameters are monitored.Examples of physiological parameters being monitored include ECG relatedsignals (e.g., heart rate), bioimpedance, respiration rates, activitylevel, and/or posture.

At step 1102, patient states are detected based on the one or morephysiological parameters. For example, patient states may includeheart-related patient states, such as various arrhythmic states (e.g.,tachycardia, bradycardia, etc.), active or resting states (based onposture, respiration rates, heart rate, activity level, etc.), andothers. Depending on the patient state detected, it may be beneficial tomonitor one or more ratios related to one or more blood concentrationlevels (e.g., oxyhemoglobin, deoxyhemoglobin, etc.). For example, forheart failure patients, it may be important to monitor oxy-Hb levelswhile the patient is exercising to ensure they do not fall belowthreshold levels. The one or more physiological signals are utilized todetect that a patient is exercising (e.g., based on one or more ofposture, heart rate, breathing rate, activity level, etc.). In responseto a detected activity level, optical signals are generated andemissions measured to calculate a ratio related to oxyhemoglobinconcentration levels. One of the benefits of increasing the level ofoptical monitoring or triggering optical monitoring based on patientstate, is resources (battery, memory, processing bandwidth, datatransmission, etc) are conserved until it is useful to monitor.

At step 1104, one or more excitation sources are utilized to illuminatetissue and one or more emission wavelengths are monitored to detect oneor more ratios related to one or more blood concentration levels.

At step 1106, a patient state is determined based on the one or moremeasured ratios and one or more physiological parameters. For example,if it is determined that the patient is exercising, and the monitoredratio indicates that oxyhemoglobin concentrations have fallen below athreshold value, this may indicate a dangerous condition for a patientwith heart failure. In response to detecting a condition such as this,at step 1108, an alert is generated and provided to the patient. Thealert may indicate the detected condition, and may provide instructionsto the patient on mitigating the risk. In other embodiments, the alertmay be communicated to an intermediate device 102 and/or remotemonitoring center for review by a physician/technical expert.

While the invention has been described with reference to an exemplaryembodiment(s), it will be understood by those skilled in the art thatvarious changes may be made and equivalents may be substituted forelements thereof without departing from the scope of the invention. Inaddition, many modifications may be made to adapt a particular situationor material to the teachings of the invention without departing from theessential scope thereof. Therefore, it is intended that the inventionnot be limited to the particular embodiment(s) disclosed, but that theinvention will include all embodiments falling within the scope of theappended claims.

The invention claimed is:
 1. A system for non-invasive monitoring ofhemoglobin concentration level, the system comprising: a medical devicecomprising: at least one light source configured to provide light topatient tissue; a first photodetector configured to monitor an emissionresponse at a first emission wavelength, wherein the first emissionwavelength is selected to correspond with a maximum of the emissionresponse of a hemoglobin component, wherein the hemoglobin componentcomprises at least one of oxyhemoglobin or de-oxyhemoglobin; and asecond photodetector configured to monitor the emission response at asecond emission wavelength, wherein the second emission wavelength isselected to correspond with a minimum of the emission response of thehemoglobin component; and one or more processors configured to receivethe emission responses at the first emission wavelength and the secondemission wavelength, wherein the one or more processors are configuredto calculate a ratio based on the received emission responses andutilize the calculated ratio to determine the hemoglobin concentrationlevel.
 2. The system of claim 1, wherein the hemoglobin component isoxyhemoglobin and the hemoglobin concentration level is an oxyhemoglobinconcentration level, wherein the first emission wavelength is selectedto correspond with a maximum of an oxyhemoglobin emission response andthe second emission wavelength is selected to correspond with a minimumof the oxyhemoglobin emission response.
 3. The system of claim 1,wherein the hemoglobin component is de-oxyhemoglobin and the hemoglobinconcentration level is a de-oxyhemoglobin concentration level, whereinthe first emission wavelength is selected to correspond with a maximumof a de-oxyhemoglobin emission response and the second emissionwavelength is selected to correspond with a minimum of thede-oxyhemoglobin emission response.
 4. The system of claim 1, whereinthe one or more processors are configured to control generation of analert in response to the hemoglobin concentration level falling below athreshold value, indicating anemia or change in the hemoglobincomponent.
 5. The system of claim 1, wherein the hemoglobinconcentration level is determined in real-time or near real-time by theone or more processors.
 6. The system of claim 1, wherein the one ormore processors are configured to collect and store a plurality ofdetermined hemoglobin concentration levels over a first monitoringperiod, and provide an output of trends in monitored hemoglobinconcentration levels.
 7. The system of claim 1, wherein the medicaldevice further includes sensors for monitoring physiological parametersassociated with the patient, including one or more of electrocardiogram(ECG) signals, respiration rates, bio-impedance levels, activity level,postures, or temperature.
 8. The system of claim 7, wherein the one ormore processors are configured to utilize at least one of the monitoredphysiological parameters in combination with stored hemoglobinconcentration levels to determine a patient condition.
 9. The system ofclaim 1, wherein the hemoglobin component comprises a first hemoglobincomponent and the ratio comprises a first ratio, the system furthercomprising a third photodetector configured to monitor the emissionresponse at a third emission wavelength, wherein the third emissionwavelength is selected to correspond with a maximum of the emissionresponse of a second hemoglobin component, and wherein the one or moreprocessors are configured to: receive the emission response at the thirdemission wavelength; calculate a second ratio based on the thirdemission response; and determine the hemoglobin concentration levelbased on a combination of the first ratio and the second ratio.
 10. Amethod of non-invasively monitoring hemoglobin concentration level, themethod comprising: providing incident light to patient tissue at a firstexcitation wavelength; monitoring an emission response at a firstemission wavelength, wherein the first emission wavelength is selectedto correspond with a maximum of the emission response of a hemoglobincomponent, wherein the hemoglobin component comprises at least one ofoxyhemoglobin or de-oxyhemoglobin; monitoring the emission response at asecond emission wavelength, wherein the second emission wavelength isselected to correspond with a minimum of the emission response of thehemoglobin component; and calculating the hemoglobin concentration levelbased on a ratio of the emission response measured at the first emissionwavelength to the emission response measured at the second emissionwavelength.
 11. The method of claim 10, wherein the hemoglobin componentis oxyhemoglobin and the hemoglobin concentration level is anoxyhemoglobin concentration level, wherein the first emission wavelengthis selected to correspond with a maximum of an oxyhemoglobin emissionresponse and the second emission wavelength is selected to correspondwith a minimum of the oxyhemoglobin emission response.
 12. The method ofclaim 10, wherein the hemoglobin component is de-oxyhemoglobin and thehemoglobin concentration is a de-oxyhemoglobin concentration, whereinthe first emission wavelength is selected to correspond with a maximumof a de-oxyhemoglobin emission response and the second emissionwavelength is selected to correspond with a minimum of thede-oxyhemoglobin emission response.
 13. The method of claim 10, furtherincluding detecting anemia based on the calculated hemoglobinconcentration level falling below a threshold level.
 14. The method ofclaim 10, wherein the monitoring and calculating a hemoglobinconcentration level is performed in real-time or near real-time.
 15. Themethod of claim 10, further including monitoring physiologicalparameters associated with the patient, including one or more ofelectrocardiogram (ECG) signals, respiration rates, bio-impedancelevels, activity level, postures, or temperature.
 16. The method ofclaim 15, further including utilizing at least one of the monitoredphysiological parameters in combination with stored hemoglobinconcentration levels to determine a patient condition.
 17. The method ofclaim 10, wherein the hemoglobin component comprises a first hemoglobincomponent and the ratio comprises a first ratio, the method furthercomprising: monitoring the emission response at a third emissionwavelength, wherein the third emission wavelength is selected tocorrespond with a maximum of the emission response of a secondhemoglobin component; and calculating a second ratio based on the thirdemission response; and wherein calculating the hemoglobin concentrationlevel comprises calculating the hemoglobin concentration level based ona combination of the first ratio and the second ratio.